Tezuka Shun, Ueno Makoto, Kobayashi Satoshi, Morimoto Manabu, Ohkawa Shinichi, Hirotani Akane, Tozuka Yuichiro, Moriya Satoshi, Nakamura Yoshiyasu, Miyagi Yohei, Sugimori Makoto, Maeda Shin
Department of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center Yokohama, Japan.
Department of Molecular Pathology and Genetics, Kanagawa Cancer Center Research Institute Yokohama, Japan.
Am J Cancer Res. 2018 Oct 1;8(10):2096-2105. eCollection 2018.
The platinum-based chemotherapy regimen FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) is currently used as a standard treatment for patients with unresectable pancreatic cancer. FOLFIRINOX is associated with severe toxicities, including neutropenia, febrile neutropenia, and anorexia; however, there are currently no reliable biomarkers to predict its efficacy and safety. Several studies of patients with various cancers have shown that tumor expression of excision repair cross-complementing (ERCC) proteins and glutathione S-transferase Pi (GSTPi) correlates with the response to platinum-based chemotherapies. Therefore, in this study, we examined the associations between expression of ERCC proteins and GSTPi and the safety and efficacy of FOLFIRINOX in 34 patients with unresectable pancreatic cancer. ERCC1, ERCC2, ERCC4, and GSTPi expression were examined by immunohistochemical staining of tumor specimens and the results were correlated with overall survival, progression-free survival, response rate, disease control rate, and the frequency of grade 3-4 neutropenia and non-hematologic toxicities. We found that ERCC1, ERCC2, ERCC4, and GSTPi were expressed in tumor samples from 64%, 24%, 18%, and 64% of patients, respectively. Notably, there were no statistically significant associations between the expression pattern of any of the proteins and either the clinical outcomes or the frequency of grade 3-4 neutropenia or grade 3-4 anorexia. Collectively, these data indicate that tumor expression of ERCC1, ERCC2, ERCC4, and GSTPi does not predict the safety or efficacy of FOLFIRINOX in patients with pancreatic cancer.
基于铂类的化疗方案FOLFIRINOX（亚叶酸钙、氟尿嘧啶、伊立替康和奥沙利铂）目前被用作不可切除胰腺癌患者的标准治疗方法。FOLFIRINOX会引发严重毒性，包括中性粒细胞减少、发热性中性粒细胞减少和厌食；然而，目前尚无可靠的生物标志物来预测其疗效和安全性。多项针对不同癌症患者的研究表明，切除修复交叉互补（ERCC）蛋白和谷胱甘肽S-转移酶Pi（GSTPi）的肿瘤表达与对铂类化疗的反应相关。因此，在本研究中，我们检测了34例不可切除胰腺癌患者中ERCC蛋白和GSTPi的表达与FOLFIRINOX安全性和疗效之间的关联。通过对肿瘤标本进行免疫组织化学染色来检测ERCC1、ERCC2、ERCC4和GSTPi的表达，并将结果与总生存期、无进展生存期、缓解率、疾病控制率以及3-4级中性粒细胞减少和非血液学毒性的发生率相关联。我们发现，ERCC1、ERCC2、ERCC4和GSTPi分别在64%、24%、18%和64%的患者肿瘤样本中表达。值得注意的是，任何一种蛋白的表达模式与临床结局、3-4级中性粒细胞减少或3-4级厌食的发生率之间均无统计学意义上的显著关联。总体而言，这些数据表明，ERCC1、ERCC2、ERCC4和GSTPi的肿瘤表达并不能预测FOLFIRINOX对胰腺癌患者的安全性或疗效。
